Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isolated dog hearts perfused with blood from a donor dogand driven at two heart rates were used to compare the effects of propranolol with those of its quaternary ammonium derivative on atrial, atrioventricular (AV) nodal, and His-Purkinje conduction. Propranolol slowed only AV-nodal conduction, increasing the minimal conduction time and the effect of prematurity, without affecting fatigue. Practolol did not have this effect. Dimethylpropranolol had similar but not identical effects on the AV node, but also slowed atrial and ventricular conduction. In contrast with the quaternary derivative of lidocaine, dimethylpropranolol's effect on atrial and ventricular conduction was not dependent on the heart rate. The effect of dimethylpropranolol on ventricular conduction was observed at doses lower than those reported by others to be antiarrhythmic.
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PMID:The effect of propranolol and dimethylpropranolol on cardiac conduction. 48 71

His-bundle electrocardiography was used to evaluate the effect of halothane on AV nodal and His-Purkinje system conduction times in the spontaneously beating dog heart. During artrial pacing at basic heart rates of 120 or 200 beats per minute (bpm), an extrastimulus (cycle length longer or shorter than that of the basic rate) was delivered to test the effect of halothane on several parameters of AV nodal conductivity. Included were the functional refractory period, basal conduction time, and fatigue effect (prolongation of basal conduction time as heart rate was increased from 120 to 200 bpm). Increasing MAC level of halothane (1.25 to 2.75 MAC) prolonged both AV node and His-Purkinje conduction times, yet had little effect on the parameters of nodal conductivity tested for. These effects of halothane could be potentially dangerous in the clinical setting for patients with defective AV conduction. In addition, changes in conduction may be in part responsible for arrhythmias seen during halothane anesthesia.
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PMID:Halothane effects on conductivity of the AV node and His-Purkinje system in the dog. 55 37

The effects of lidocaine and methyl lidocaine on cardiac conduction were studied using His bundle recordings from isolated blood perfused dog hearts. The input and output characteristic of the atrioventricular (AV) node can be described as consisting of three components, namely, minimal conduction time, fatigue, and the effect of prematurity (deltaCT). Lidocaine (2.5-10.0 mg/kg) increased minimal conduction time but not fatigue. Methyl lidocaine (1.25-5.0 mg/kg) increased both. A dose of 5 mg/kg or less of either drug caused a nonparallel shift of the deltaCT curve to the right. High doses of lidocaine (10 mg/kg) cause deltaCT to become rate-dependent. Lidocaine slowed atrial conduction only slightly. Atrial block prevented the observation of the effect of methyl lidocaine in doses higher than 5.0 mg/kg. Both drugs showed greater effect on atrial conduction at fast heart rate. Lidocaine did not affect ventricular conduction time at slow heart rates and had only minimal effects at fast heart rates. Methyl lidocaine increased ventricular conduction time at all heart rates. The results of this study indicate that lidocaine and methyl lidocaine have entirely different spectra of activity on cardiac conduction, in that their effect on AV nodal conduction do not differ greatly whereas the quaternary analog has a much stronger depressant effect on atrial and ventricular conduction.
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PMID:Effect of lidocaine and methyl lidocaine on cardiac conduction. 85 Jan 38

Recent work has shown that alterations in the dynamic atrioventricular (AV) nodal response to changes in heart rate can significantly modify AV nodal function. The present study was designed to evaluate the nature and potential importance of sympathetic regulation of the rate-dependent properties of the AV node. Selective stimulation protocols and mathematical formulations were used to independently quantify AV nodal recovery, facilitation, and fatigue in 12 morphine-chloralose-anesthetized dogs. Vagal effects were prevented by bilateral vagal transection and intravenous atropine, and the sinus node was crushed to allow a broader range of pacing cycle lengths. In seven dogs with sympathetic nerves intact, beta-adrenergic receptor blockade increased the recovery time constant (tau rec) for the conduction of premature test beats from 47 +/- 2 (mean +/- SEM) msec (control) to 62 +/- 1 msec (p less than 0.001), whereas isoproterenol decreased tau rec to 38 +/- 1 msec (p less than 0.001). In addition, beta-blockade increased the maximum amount of rate-dependent AV nodal fatigue from 7 +/- 1 msec (at a cycle length of 198 +/- 9 msec [control]) to 17 +/- 2 msec (p less than 0.001). In five dogs with decentralized stellate ganglia, tau rec was decreased from 71 +/- 3 msec (control) to 57 +/- 4 msec and 48 +/- 2 msec (p less than 0.001 for each) by left stellate ganglion stimulation at 5 and 10 Hz, respectively. Maximum fatigue was similarly reduced from 16 +/- 1 msec (control) to 12 +/- 2 msec (p = NS) and 8 +/- 1 msec (p less than 0.01), respectively. Stellate ganglion stimulation, isoproterenol, and beta-blockade did not alter AV nodal facilitation. A mathematical model incorporating quantitative indexes of AV nodal function accurately accounted for tachycardia-dependent increases in the atrial-His activation interval, which were enhanced by beta-adrenergic receptor blockade and reduced by isoproterenol. Furthermore, this model showed that beta-adrenergic effects were increased by increasing heart rate, with the majority of the rate-dependent action being due to changes in the time course of AV nodal recovery. We conclude that beta-adrenergic receptor stimulation alters functional properties that govern the AV nodal response to changes in heart rate. These changes in functional properties alter the ability of the AV node to conduct impulses during tachycardia and, as such, could play a major role in the ability of sympathetic stimulation to promote and beta-adrenergic receptor blockade to prevent the occurrence of AV nodal reentrant arrhythmias.
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PMID:Effects of beta-adrenergic receptor stimulation and blockade on rate-dependent atrioventricular nodal properties. 134 76

The roles of changes in refractory and recovery properties of the atrioventricular node as affected by facilitation and fatigue in the genesis of Wenckebach periodicity were studied in isolated rabbit heart preparations. The contribution of nodal recovery time, facilitation, and fatigue to beat-to-beat changes in nodal conduction time (NCT) and effective (ERPN) and functional refractory periods of node (FRPN) occurring during stable 4:3 Wenckebach cycles was determined with premature stimulation protocols performed during these cycles. Fatigue prolonged, equally for each beat, NCT, ERPN, and FRPN, and therefore did not contribute to Wenckebach periodicity. Beat-to-beat increases in facilitation broadened the range of recovery times for which conduction was successful and decreased NCT, ERPN, and FRPN below the values expected from fatigue alone. However, ERPN and NCT increased overall from beat to beat because of NCT-induced (effects of NCT on ensuing refractoriness) increases in nodal refractoriness and consequent shortenings of the recovery time. These findings establish a complementary role for the recovery and refractory properties in generating the Wenckebach periodicity and demonstrate the modulating roles of facilitation and fatigue on this phenomenon.
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PMID:Beat-to-beat changes in AV nodal refractory and recovery properties during Wenckebach cycles. 162 46

A number of functional properties of the atrioventricular (AV) node have been described in response to changes in the atrial input rate. The purpose of this study was 1) to develop quantitative descriptors of these properties, and 2) to determine whether they can account for rate-dependent changes in AV nodal conduction. The delay in AV nodal conduction of single premature beats (recovery) was found to be an exponential function of coupling interval with a time constant of 66 +/- 2 (+/- SE) ms. A single abbreviated (facilitation) cycle did not alter the time constant of recovery or basal conduction for a subsequent beat but shifted its recovery curve to the left to an extent exponentially related to the facilitation cycle length. The induction of a tachycardia with HA interval fixed so as to control the recovery and facilitation variables resulted in a first-order onset of AV conduction slowing (fatigue). The fatigue process had a time constant in the range of 70 beats and a magnitude that was a decaying exponential function of HA interval. An equation incorporating quantitative descriptors of recovery, facilitation, and fatigue accurately predicted rate-dependent changes in AH interval. We conclude that 1) the AV nodal properties of recovery, facilitation, and fatigue are amenable to quantitative characterization, and 2) rate-dependent changes in AV nodal conduction time can be well described in terms of these underlying properties.
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PMID:Quantitation of dynamic AV nodal properties and application to predict rate-dependent AV conduction. 187 57

Lymph nodes were examined from four patients with incipient adult T-cell leukemia-lymphoma (ATLL) who had mild lymphadenopathy, fatigue, no or a few atypical lymphocytes in their peripheral blood, and integrated proviral human T-cell lymphotrophic virus type I (HTLV-I) DNA in the nodes. The HTLV-I DNA was detected by southern blot analysis and/or polymerase chain reaction in the lymph nodes of all cases. The nodal architecture was preserved. Some scattered or aggregated highly lobular, cerebriform, or Reed-Sternberg-like giant cells were observed, with occasional mitoses and diffuse infiltration of small to medium-sized lymphocytes, with no or minimal nuclear abnormalities in the enlarged paracortex. The giant cells were usually positive for Ki-1 and also for UCHL-1 and other T-cell markers but negative for Ber-H2. Rearrangement and/or deletion of T-cell receptors were found in three of four patients. All patients died within 2 years, with transformation to overt leukemia-lymphoma occurring in three patients, and pulmonary carcinoma in one. The incipient or prelymphomatous phase of ATLL should be differentiated from Hodgkin's disease because of the distinctly different prognoses of these two diseases.
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PMID:Lymph nodes in incipient adult T-cell leukemia-lymphoma with Hodgkin's disease-like histologic features. 200 51

The atrioventricular (AV) node responds in a complex fashion to changes in activation rate. A variety of approaches have been used to explain these dynamic AV nodal responses, but none has been able to account fully for AV nodal behavior. Three specific rate-dependent properties of the AV node have been described: 1) time-dependent recovery after excitation, 2) an effect of short cycles to advance recovery ("facilitation"), and 3) a gradual slowing of conduction in response to sustained, high-frequency activation ("fatigue"). We hypothesized that a model incorporating quantitative descriptors of all three processes might be able to account for a wide variety of AV nodal behaviors. Quantitative descriptors of AV nodal recovery, facilitation, and fatigue were developed based on AV nodal conduction changes during selective pacing protocols in seven autonomically blocked dogs. These descriptors were incorporated into a set of mathematical equations that define AV nodal conduction of any beat based on activation history. The equations were then applied to predict pacing-induced Wenckebach periodicity in each dog. Experimental data were obtained after nine to 19 step decreases in atrial cycle length into the Wenckebach zone in each animal. Observed behaviors included complex patterns of block, a progressive increase in the level of block over 5 minutes of rapid pacing, and periods of alternating patterns of block. The model accurately predicted the onset of AV block at each cycle length, the relation between conduction ratio and cycle length as a function of time, and the changing patterns of Wenckebach periodicity during sustained atrial pacing. All three terms of the model equation (describing recovery, facilitation, and fatigue) were essential to account fully for the observed behaviors. Elimination of AV nodal fatigue from the model resulted in failure to account for time-dependent changes in Wenckebach patterns, whereas exclusion of facilitation led to consistent overestimation of the degree of AV block at each cycle length. We conclude that a mathematical model incorporating terms to describe recovery, facilitation, and fatigue accurately predicts a wide range of Wenckebach-type behavior and that complex conduction patterns of the AV node can be fully accounted for by simple functional AV nodal properties.
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PMID:A unified model of atrioventricular nodal conduction predicts dynamic changes in Wenckebach periodicity. 201 92

Vagal effects on atrioventricular (AV) nodal conduction are accentuated by increases in heart rate. To establish the mechanism of these rate-dependent negative dromotropic actions, we studied the properties governing AV nodal adaptation to changes in heart rate in chloralose-anesthetized dogs in the absence and presence of bilateral cervical vagal nerve stimulation (20 Hz, 0.2 msec). Stimulation protocols were applied to evaluate the contributions of changes in AV nodal recovery, facilitation, and fatigue independently of each other. Vagal stimulation slowed AV nodal recovery in a voltage-dependent way, increasing the time constant of recovery (tau r) from 80 +/- 7 to 194 +/- 16 msec (mean +/- SEM, p less than 0.01) at the highest voltage studied. The facilitating effect of a premature (A2) beat was manifested by a leftward shift of the recovery curve (A3H3 versus H2A3) of a subsequent A3 beat. The magnitude of shift depended on the A1A2 coupling interval and was reduced by vagal stimulation at all A1A2 intervals (maximum shift: control, 63 +/- 12 msec; vagus, 24 +/- 11 msec; p less than 0.01). When recovery and facilitation were kept constant, abrupt increases in AV nodal activation rate caused a slow (tau = 75 beats) increase in AH interval (fatigue). Vagal stimulation increased the magnitude of this process (maximum: control, 11 +/- 2 msec; vagus, 27 +/- 3 msec; p less than 0.001), without altering its time course. At activation rates comparable to sinus rhythm in humans, vagal stimulation at an intermediate voltage increased the AH interval by 25 msec. As heart rate increased, vagally induced changes in dynamic processes amplified AH prolongation up to fivefold at maximum rate. The role of vagal changes in individual functional properties depended on heart rate, but slowing of recovery was the single most important factor, constituting over 50% of overall vagal action at rapid rates. We conclude that vagal stimulation alters the ways in which the AV node responds to changes in activation rate and that at rapid rates most of the negative dromotropic action of the vagus is due to changes in the AV nodal response to tachycardia. Alterations in rate-dependent AV nodal properties are a novel and potentially important mechanism through which interventions may affect AV nodal conduction.
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PMID:Vagal modulation of the rate-dependent properties of the atrioventricular node. 217 1

Ninety-seven evaluable patients with measurable, advanced, malignant melanoma were treated with recombinant alpha interferon in a cooperative phase II efficacy trial, whose primary objective was to estimate the response rate. Interferon (rIFN alpha-2a, Roferon-A) was injected subcutaneously daily for 70 days. Dose was escalated in four steps from three million units to 36 million units over ten days. Eight patients responded objectively and six patients (6%) had a complete response. The median duration of complete response was 11 months. Patients achieving complete response had only cutaneous, nodal, or pulmonary disease; some had extensive prior therapy; some could tolerate no more than three million units per day. Few patients could tolerate the target dose of 36 million units daily for 70 days. Limiting toxicity was primarily fatigue. Interferon in tolerable doses is effective in a small subset of patients with melanoma. Comparison of published trials of dacarbazine and recombinant alpha interferon indicates the two drugs have similar activity.
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PMID:Phase II study of recombinant alpha-interferon in malignant melanoma. 223 1


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